Trial record 2 of 12 for:    "Multicentric Castleman’s Disease"

A Study to Evaluate the Efficacy and Safety of CNTO328 Plus Best Supportive Care in Multicentric Castleman's Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01024036
First received: November 30, 2009
Last updated: August 1, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to demonstrate that CNTO 328 when administered in combination with best supportive care (BSC) is superior to BSC in terms of durable tumor and symptomatic response (complete response or partial response) among patients with Multicentric Castleman's Disease.


Condition Intervention Phase
Multicentric Castleman's Disease
Drug: Siltuximab
Drug: Placebo
Drug: Best Supportive Care (BSC)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo Controlled Study to Assess the Efficacy and Safety of CNTO 328 (Anti IL 6 Monoclonal Antibody) Plus Best Supportive Care Compared With Best Supportive Care in Subjects With Multicentric Castleman's Disease

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Percentage of Participants Who Achieved Durable Tumor and Symptomatic Response - by Independent Radiology Review [ Time Frame: From Day 1 of Cycle 1 of treatment with study medication until treatment failure or discontinuation of treatment or withdrawal from the study, or up to 48 weeks after the last participant started study medication, whichever occurred earlier ] [ Designated as safety issue: No ]
    Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: >=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks. The statistical analysis shows difference in symptomatic response rate (siltuximab+best supportive care [BSC] minus Placebo+BSC).


Secondary Outcome Measures:
  • Median Duration of Tumor and Symptomatic Response - by Independent Radiology Review [ Time Frame: From the date when durable tumour and symptomatic response is achieved until treatment failure, as assessed until 48 weeks after the last participant started study treatment ] [ Designated as safety issue: No ]
    Duration of tumor and symptomatic response is defined as time from first documentation of tumor and symptomatic response (CR or PR) to treatment failure. Whenever possible, treatment failure documented by the appearance of new lesions should be confirmed by histologic examination of the new lesions. Symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: >=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks.

  • Percentage of Participants Who Achieved Complete Response (CR) + Partial Response (PR) (Tumor Response Rate) - by Independent Radiology Review [ Time Frame: From Day 1 of Cycle 1 until the date when durable tumour and symptomatic response is achieved, as assessed up to 48 weeks after the last participant started study treatment ] [ Designated as safety issue: No ]
    Overall tumor response is CR + PR assessed according to Cheson criteria. CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion). PR: a >=50 percent decrease in sum of the product of the diameters of index lesion(s), with at least stable disease in all other evaluable disease. Statistical analysis shows difference of overall response rates (siltuximab+best supportive care [BSC] minus Placebo+BSC).

  • Median Duration of Tumor Response - by Independent Radiology Review [ Time Frame: From the date when tumour response is achieved until tumour progression, as assessed up to 48 weeks after the last participant started study treatment ] [ Designated as safety issue: No ]
    Duration of tumor response is defined as time from first documentation of tumor response to tumor progression. Tumour response is complete response (CR) + partial response (PR) as assessed according to Cheson criteria. CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion). PR: a >=50 percent decrease in sum of the product of the diameters of index lesion(s), with at least stable disease in all other evaluable disease. Statistical analysis shows difference of overall response rates (siltuximab+best supportive care [BSC] minus Placebo+BSC).

  • Time to Treatment Failure [ Time Frame: From the date of randomization until a participant fails treatment, as assessed up to 48 weeks after the last participant started study treatment, whichever occurred earlier ] [ Designated as safety issue: No ]
    Time to treatment failure was defined as the time from randomization until the participant fails treatment. Treatment failure was defined as any of the following: a sustained increase from baseline in disease related symptoms >=Grade 2 persisting for at least 3 weeks despite best supportive care (BSC); onset of any new disease related Grade 3 or higher symptom despite BSC; sustained (ie, at least 3 weeks) deterioration in performance status (increase from baseline in Eastern Cooperative Oncology Group Performance Status by more than 1 point) despite BSC; radiologic progression, as measured by modified Cheson criteria; Initiation of any other therapy intended to treat multicentric Castleman's disease ie, prohibited treatments. Statistical analysis shows difference in treatment failure rate (siltuximab+BSC minus Placebo+BSC).

  • Percentage of Participants Who Achieved >= 15 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate) [ Time Frame: Week 13 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Achieved >= 20 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate) [ Time Frame: Week 13 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Discontinued Corticosteroids [ Time Frame: From Day 1 of Cycle 1 until 48 weeks after the after the last participant started study treatment ] [ Designated as safety issue: No ]
    Percentage of participants who discontinued corticosteroids during blinded treatment period and who were dependent on corticosteroids at baseline (Day 1 of Cycle 1).

  • 1-year Survival Rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Median Time Required to Achieve >=1 Point Decrease in the Multicentric Castleman's Disease Symptom Scale (MCD-SS) Score From Baseline [ Time Frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment ] [ Designated as safety issue: No ]
    A patient-reported symptom scale. Symptom presence/absence and severity are noted on an anchor-based numeric scale. Scores range from 1 (very mild) to 5 (very severe).

  • Median Time Required to Achieve >=3-point Increase in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores From Baseline [ Time Frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment ] [ Designated as safety issue: No ]
    The FACIT-F, a 13-item instrument, was designed to measure patient-reported fatigue. It is one of the suite of FACIT instruments developed for outcomes in cancer. Concepts measured in the scale include tiredness, weakness, and difficulty conducting usual functional activities or social interaction due to fatigue. Response options range from "not at all" (0) to "very much" (4), and yield a summary score. Total FACIT-F score is the sum of 13 items, ranging from 0 (not at all) to 52 (very much). Higher scores represent better outcomes.

  • Median Time Required to Achieve >=5-point Increase in the Short-Form-36 (SF-36) Physical Component Summary (PCS) Scores From Baseline [ Time Frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment ] [ Designated as safety issue: No ]
    SF-36 is a questionnaire and PCS is a part of subscle assessing physical functioning, role-physical, bodily pain, and general health. The scores range from 0 (worst score) to 100 (best score), with a higher score indicating better quality of life.


Enrollment: 79
Study Start Date: March 2010
Estimated Study Completion Date: February 2017
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Siltuximab+best supportive care (BSC)
Siltuximab 11 mg/kg will be administered as a 1-hour intravenous infusion every 3 weeks + BSC.
Drug: Siltuximab
Siltuximab 11 mg/kg will be administered by 1-hour intravenous infusion every 3 weeks
Other Name: CNTO 328
Drug: Best Supportive Care (BSC)
BSC included treatment for effusions, antipyretics, antipuretics, antihistamines, pain medication, treatment for infections, transfusions, management of infusion-related reactions, and corticosteroids.
Placebo Comparator: Placebo+BSC
Placebo will be administered as a 1-hour intravenous infusion every 3 weeks + BSC. Participants who do not respond to placebo during the blinded treatment period will have option to crossover and receive siltuximab 11 mg/kg which will be administered by 1-hour intravenous infusion every 3 weeks + BSC during the unblinded treatment period.
Drug: Placebo
Placebo will be administered by 1-hour intravenous infusion every 3 weeks
Drug: Best Supportive Care (BSC)
BSC included treatment for effusions, antipyretics, antipuretics, antihistamines, pain medication, treatment for infections, transfusions, management of infusion-related reactions, and corticosteroids.

Detailed Description:

This is a multicenter (study conducted at multiple sites), randomized (the study medication is assigned by chance), double blind (neither investigator nor the participant knows the treatment that the participant receives), placebo controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study), study to assess the efficacy and safety of CNTO 328 plus BSC compared with BSC in patients with symptomatic Multicentric Castleman's Disease. The study mainly consists of 3 phases, including: the screening phase (majority of assessments performed within 28 days of first dose), the treatment phase (blinded and unblinded), and the follow up phase. In the blinded treatment phase, approximately 78 patients will be randomly assigned in 1:2 ratios to either of 2 treatment groups, ie, Placebo + BSC, or CNTO 328 + BSC. Participants receiving placebo + BSC during blinded treatment period who do not respond and have treatment failure will have the option to crossover and receive siltuximab + BSC during unbllinded treatent period. The follow up phase will be 3 months after last dose of study medication and the survival will be followed up until the study ends. Safety evaluations for adverse events, clinical laboratory tests, electrocardiogram, vital signs, patient-recorded temperature, and physical examination will be monitored throughout the study. The total study duration will be 5 years after the last patient starts study medication.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Measurable and symptomatic Multicentric Castleman's Disease
  • Adequate organ function as assessed by laboratory values evaluated by the investigator to determine eligibility prior to treatment
  • Eastern Cooperative Oncology Group performance status of 0, 1, or 2
  • Corticosteroids dose that does not exceed 1 mg/kg/day of prednisone, and has remained stable or decreased over the 4 weeks before treatment

Exclusion Criteria:

  • Human Immunodeficiency Virus or Human Herpes Virus-8 positive
  • Skin lesions as sole measurable manifestation of Multicentric Castleman's Disease
  • Previous history of lymphoma
  • Malignancies, except for adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or cancer other than lymphoma, from which the patient has been disease-free for 3 or more years
  • Concurrent medical condition or disease that may interfere with study participation
  • Prior exposure to Interleukin-6 or Interleukin-6 receptor targeted therapies
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01024036

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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided by Janssen Research & Development, LLC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01024036     History of Changes
Other Study ID Numbers: CR016705, CNTO328MCD2001, 2009-012380-34
Study First Received: November 30, 2009
Results First Received: May 16, 2014
Last Updated: August 1, 2014
Health Authority: United States: Food and Drug Administration
Germany: Ethics Commission
Great Britain: Medicines and Healthcare Products Regulatory Agency
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Taiwan: Department of Health

Keywords provided by Janssen Research & Development, LLC:
Multicentric Castleman's Disease
MCD
CNTO 328
Best Supportive Care
Tumor
Symptomatic response
Pharmacokinetics
Interleukin-6
IL6

Additional relevant MeSH terms:
Giant Lymph Node Hyperplasia
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014